Bioequivalence and Bioavailability Forum

Lessons learned? [Regulatives / Guidelines]

posted by Helmut  – Vienna, Austria, 2011-08-24 15:51 (5012 d 17:14 ago) – Posting: # 7304
Views: 7,248

Dear control freaks!

❝ Second I come more and more to the conclusion that a decomposition of the subject effect into the terms sequence and subject nested within sequence is not really possible with those crippled datasets […]. The robust model without any peculiarities should therefore include period and subject effects only.

❝ Do I err here?

If you want to get a second amateur’s opinion: exactly. That’s why I called the datasets (after removal of T!) ‘crippled’. All information about sequences (RTRT _^ TRTR ¬ RR!) is lost. Martin (not an amateur) once told me that you can do only statistics if you understand the data generating process. In all replicate datasets I have seen until now, EMA’s method gives a smaller CV_WR than the full model (= FDA’s or EMA’s ‘Method C’). Politics = narrower AR? If we throw away sequences, it doesn’t make any sense to include them in the model (not to speak about nested subjects either).

BTW, more than 20 years after Freeman’s paper¹, Senn’s book², and the empiric study by D’Angelo et al.³ EMA has realised (see IR GL) that sequence effects are of no importance in a properly designed cross-over study. But: Would anybody evaluate a 2×2 cross-over by Y=treatment+period+subject only - though the CI stays the same?

Agree with your third point.

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Quotes on a sad occasion:

• Ein Klavier, ein Klavier! Mutter, wir danken dir!
  
• In der Politik gibt niemals der Klügere nach,
  sondern immer der Schwächere…

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1. Freeman PR. The Performance of the Two-Stage Analysis of Two-Treatment, Two-Period Crossover Trials. Stat Med. 1989;8:1421–32.
   
2. S Senn S. Cross-over Trials in Clinical Research. Chichester: John Wiley & Sons; 2^nd ed. 2002.
   
3. D’angelo G, Potvin D, Turgeon J. Carry-Over Effects in Bioequivalence Studies. J Biopharm Stat. 2001;11(1&2):35–43.

—
Dif-tor heh smusma 🖖🏼 Довге життя Україна! 
Helmut Schütz


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Complete thread:

• EMA replicate surprise d_labes 2011-08-23 13:01 [Regulatives / Guidelines] 
  • EMA replicate surprise ElMaestro 2011-08-23 13:15
    • Big bäng CV d_labes 2011-08-23 13:58
      • Big bäng CV ElMaestro 2011-08-23 15:02
        • Period DFs d_labes 2011-08-23 15:28
          • Period DFs Helmut 2011-08-23 15:36
          • Period DFs ElMaestro 2011-08-23 16:26
          • Period DFs ElMaestro 2011-08-23 16:58
            • Period DFs Helmut 2011-08-24 00:44
              • Lessons learned? d_labes 2011-08-24 11:24
                • Lessons learned?Helmut 2011-08-24 13:51
                • Lessons learned? ElMaestro 2011-08-28 21:34
            • Period DFs - EMA code literally in R d_labes 2011-08-24 10:47
              • Period DFs - EMA code literally in R ElMaestro 2011-08-24 13:04
                • call for expert’s opinions Helmut 2011-08-24 14:01
                  • call for expert’s opinions jdetlor 2011-11-01 03:05
                    • The finance sector ElMaestro 2011-11-02 09:48